Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
권호 표지
DOI QR코드

DOI QR Code

Calcitonin Transport through Skin Using Iontophoresis

  • Received : 2010.12.01
  • Accepted : 2010.12.18
  • Published : 2011.02.20
Download PDF
⟨ Previous Next ⟩

Abstract

The objective of this work is to study transdermal delivery of calcitonin using iontophoresis and to evaluate various factors which affect the transdermal transport. We have studied the effect of polarity, current density, drug concentration, penetration enhancers (isopropyl myristate [IPM] and ethanol) and laser treatment on transdermal flux and the results were compared. We also investigated the iontophoretic flux from microemulsions containing calcitonin together with oleic acid (OA) or IPM. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell and full thickness hairless mouse skin. Anodal delivery at pH 3.0 was much larger than cathodal and passive delivery, due to the positive charge of calcitonin. Cumulative amount delivered (CUM) by cathodal or passive delivery was close to zero for 10 hours. The pretreatment of skin by neat IPM markedly increased the CUM anodically. CUM increased as the current density, drug concentration or the duration of IPM treatment increased. Microemulsion containing IPM or oleic acid was prepared and the phase diagram was constructed. CUM also increased when IPM was incorporated into a microemulsion. OA microemulsion showed similar enhancing effect to IPM microemulsion. The delivery of calcitonin from 70% (v/v) ethanol aqueous solution showed a large increase in flux. Laser treatment of skin before flux experiment exhibited about 2 fold increase in total calcitonin amount transported for 12 hours, when compared to that delivered by IPM microemulsion. Based on these results, we have evaluated the possibility of delivering enough amount of calcitonin to reach the therapeutic level. The data suggest that it is highly possible to deliver clinically effective amount of calcitonin using iontophoresis patch with small area (<10 $cm^2$).

Keywords

References

  1. Bhatia, K.S., Gao, S., Singh. J., 1997. Effect of penetration enhancers and iontophoresis on the FT-IR spectroscopy and LHRH permeability. J. Control. Rel. 47, 81-89. https://doi.org/10.1016/S0168-3659(96)01618-5
  2. Bommannan, D., Potts, R.O., Guy, R.H., 1991. Examination of the effect of ethanol on human stratum corneum using infrared spectroscopy. J. Control. Rel. 16, 299-304. https://doi.org/10.1016/0168-3659(91)90006-Y
  3. Chandra, A., Sharma, P.K., Irchhiaya, R., 2009. Microemulsionbased hydrogel formulation for transdermal delivery of dexamethasone. Asian. J. Pharmaceutics. 3(1), 30-36. https://doi.org/10.4103/0973-8398.49172
  4. Delgado-Charro, M.B., Iglesias-Vilas, G., Blanco-Mendez, J., Lopez-Quintela, M.A., Marty, J.P., Guy, R.H., 1997. Delivery of a hydrophilic solute through the skin from novel microemulsion systems. Eur. J. Pharm. Biopharm. 43, 37-42. https://doi.org/10.1016/S0939-6411(96)00016-1
  5. Francoeur, M.L., Golden, G.M., Potts, R.O., 1990. Oleic acid: Its effects on stratum corneum in relation to (trans)dermal drug delivery. Pharm. Res. 7, 621- 627. https://doi.org/10.1023/A:1015822312426
  6. Ghanem, A.H., Mahmoud, H., Higuchi, W.I., Rohr, U.D., Borsadia, S., Liu, P., Fox, J., Good, W., 1987. The effects of ethanol on the transport of a-estradiol and other permeants in hairless mouse skin II. A New quantitative approach. J. Control. Rel. 6, 75-83. https://doi.org/10.1016/0168-3659(87)90065-4
  7. Goodman M., Barry, B.W., 1988. Action of penetration enhancers on human skin as assessed by the permeation of model drugs 5-fluorouracil and estradiol. I. Infinite dose technique. J. Invest. Dermatol. 91, 323-327. https://doi.org/10.1111/1523-1747.ep12475655
  8. Green, P.G., Hinz, R.S., Kim, A., Cullander C., Yamane G., Szoka Jr., F.C., Guy, R.H., 1992. Transdermal iontophoresis of amino acids and peptides in vitro, J. Control. Rel. 21(1-3), 187-190. https://doi.org/10.1016/0168-3659(92)90020-R
  9. Heit, M.C., Riviere, J.E., 1997. Electrically-Assisted transdermal drug delivery. Pharm. Res. 14(6), 687-761. https://doi.org/10.1023/A:1012129801406
  10. Huwyler, R., Born, W., Ohanhaus, E.E., Fischer, J.A., 1979 Plasma kinetics and urinary excretion of exogenous human and salmon calcitonin in man. Am. J. Physiol. 236, E15–E19
  11. Ibrahim, S.A., Li, S.K., 2010. Chemical enhancer solubility in human stratum corneum lipids and enhancer mechanism of action on stratum corneum lipid domain. Int. J. Pharm. 383, 89-98. https://doi.org/10.1016/j.ijpharm.2009.09.014
  12. Jacques, S.L., McAuliffe, D.J., Irvin, B.S., Blank, I.H., Parrish, J.A., 1987. Controlled removal of human stratum corneum by pulsed laser. J. Invest. Dermatol. 88, 88-93. https://doi.org/10.1111/1523-1747.ep12465112
  13. Jiang, S.J., Hwang, S.M., Choi, E.H., Elias, P.M., Ahn, S.K., Lee, S.H., 2000. Structural and functional effects of oleic acid and iontophoresis on hairless mouse stratum corneum. J. Invest. Dermatol. 114, 64-70. https://doi.org/10.1046/j.1523-1747.2000.00834.x
  14. Jung, S.A., Gwak, H.S., Chun, I.K., Oh, S.Y., 2008. Iontophoretic Delivery of Levodopa: Permeation Enhancement by Oleic Acid Microemulsion and Ethanol. J. Kor. Pharm. Sci. 38(6), 373-380.
  15. Kigasawa, K., Kajimoto, K., Hama, S., Saito, A., Kanamura, K., Kogure, K., 2010. Noninvasive delivery of siRNA into the epidermis by iontophoresis using an atopic dermatitis-like model rat. Int. J. Pharm. 383, 157-160. https://doi.org/10.1016/j.ijpharm.2009.08.036
  16. Kreilgaard, M., 2002. Influence of microemulsions on cutaneous drug delivery. Adv. Drug Deliv. Rev. 54, S77-S98. https://doi.org/10.1016/S0169-409X(02)00116-3
  17. Lamprecht A,, Yamamoto H., Takeuchi H., Kawashima Y., 2004. pH-sensitive microsphere delivery increases oral bioavailability of calcitonin. J. Control. Rel. 98(1), 1-9. https://doi.org/10.1016/j.jconrel.2004.02.001
  18. Leduc, S., 1908. Electric ions and their use in medicine. Rebman Ltd, London.
  19. Lee, W.R., Shen, S.C., Wang, K.H., Hu, C.H., Fang, J.Y., 2002. The effect of Laser treatment on skin to enhance and control transdermal delivery of 5-flurouracil. J.Pharm. Sci. 91 (7), 1613-26. https://doi.org/10.1002/jps.10142
  20. Loftsson, T., Gildersleeve, N., Bodor, N., 1989. Effect of choline esters and oleic acid on the penetration of acyclovir, estradiol, hydrocortisone, nitroglycerin, retinoic acid and trifluorothymidine across hairless mouse skin in vitro. Acta. Pharm. Nord. 1, 279-286.
  21. Marcells, G.N., Ellis, D.A.F., 2000. Laser facial skin resurfacing: discussion on erbium:YAG and CO2 lasers. J. Otolaryngol. 29, 78–82.
  22. Matsuyama, T., Morita, T., Horikiri, Y., Yamahara, H., Yoshino, H., 2006. Improved nasal absorption of salmon calcitonin by powdery formulation with N-acetyl-L-cysteine as a mucolytic agent. J. Control. Rel. 115(2), 183-188. https://doi.org/10.1016/j.jconrel.2006.08.004
  23. Nair, V.B., Panchagnula, R., 2003. Effect of iontophoresis and fatty acids on permeation of arginine vasopressin through rat skin. Pharmacol. Res. 47(6), 563-569. https://doi.org/10.1016/S1043-6618(03)00016-1
  24. Nakamura K., Kazuya K., Mori K., Higo N., Sato S., Yamamoto K., 2001. Transdermal administration of salmon calcitonin by pulse depolarization-iontophoresis in rats. Int. J. Pharm. 218(1-2), 93-102. https://doi.org/10.1016/S0378-5173(01)00615-9
  25. Ongpipattanakul, B., Burnette, R.R., Potts, R.O., Francoeur, M.L., 1991. Evidence that oleic acid exists in a separate phase within stratum corneum lipids. Pharm. Res. 8(3), 350-354. https://doi.org/10.1023/A:1015845632280
  26. Patel, S., Lyons, A.R., Hosking, D.J., 1993. Drugs used in the treatment of metabolic bone diseases. Drugs. 46, 594–617
  27. Pillai, O., Nair, V., Panchagnula, R., 2004. Transdermal iontophoresis of insulin: IV. Influence of chemical enhancers. Int. J. Pharm. 269, 109-120. https://doi.org/10.1016/j.ijpharm.2003.09.032
  28. Potts, R.O., Tamada, J.A., Tierny M.J., 2002. Glucose monitoring by reverse iontophoresis. Diabetes. Metab. Res. rev. 18(S1), S49-S63. https://doi.org/10.1002/dmrr.210
  29. Power, I., 2007. Fentanyl HCl iontophoretic transdermal system (ITS): clinical application of iontophoretic technology in the management of acute postoperative pain. Br. J. Anaesth. 98(1), 4-11. https://doi.org/10.1093/bja/ael314
  30. Batheja, P., Thakur, R., Michniak, B., 2006. Transdermal iontophoresis. Expert Opin. Drug Deliv. 3(1), 127-138. https://doi.org/10.1517/17425247.3.1.127
  31. Ramachandran, C., Fleisher, D., 2000. Transdermal delivery of drugs for the treatment of bone diseases. Adv. Drug Deliver. Rev. 42, 197-223. https://doi.org/10.1016/S0169-409X(00)00062-4
  32. Reginster, J.Y., 1993. Calcitonin for prevention and treatment of osteoporosis. Am. J. Med. 95(5A), 44S-47S. https://doi.org/10.1016/0002-9343(93)90382-Y
  33. Sinha V.R., Maninder P.K., 2000. Permeation Enhancers for Transdermal Drug Delivery. Drug Dev. Ind. Pharm. 26(11), 1131-1140. https://doi.org/10.1081/DDC-100100984
  34. Sintov, A.C., Brandys-Sitton, R., 2006. Facilitated skin penetration of lidocaine: combination of a short-term iontophoresis and microemulsion formulation. Int. J. Pharm. 316(1-2), 58-67. https://doi.org/10.1016/j.ijpharm.2006.02.034
  35. Subedi, R.K., Oh, S.Y., Chun, M.K., Choi, H.K., 2010. Recent advances in transdermal drug delivery. Arch. Pharm. Res. 33, 339-351. https://doi.org/10.1007/s12272-010-0301-7
  36. Suh, H., Jun, H.W., 1996. Effectiveness and mode of action of isopropyl myristate as a permeation enhancer for naproxen through shed snake skin. J. Pharm. Pharmacol. 48, 812-816. https://doi.org/10.1111/j.2042-7158.1996.tb03979.x
  37. Suwanpidokkul, N., Thongnopnua, P., Umprayn, K., 2004. Transdermal delivery of zidovudine (AZT): the effects of vehicles, enhancers, and polymer membranes on permeation across cadaver pig skin. AAPS PharmSciTech. 5(3), 48.
  38. Tascioglu, F., Colak, O., Armagan, O., Alatas, O., Oner, C., 2005. The treatment of osteoporosis in patients with rheumatoid arthritis receiving glucocorticoids: a comparison of alendronate and intranasal salmon calcitonin. Rheumatol. Int. 26(1), 21-9. https://doi.org/10.1007/s00296-004-0496-3
  39. Thevenin, M.A., Grossiord, J.L., Poelman, M.C., 1996. Sucrose esters/co-surfactant ME systems for transdermal delivery: assessment of bicontinuous structures. Int. J. Pharm. 137, 177-186. https://doi.org/10.1016/0378-5173(96)04518-8
  40. Zempsky W.T., Anand K.J.S., Sullivan, K.M., Fraser, D., Cucina, K., 1998. Lidocaine iontophoresis for topical anesthesia before intravenous line placement in children. J. Pediatrics. 132(6), 1061-1063. https://doi.org/10.1016/S0022-3476(98)70413-5